A Comprehensive Study on Ruptured Liver Abscess in a Tertiary Care Center

Background Bacteria and parasites cause liver abscesses (LAs), with the unusual but fatal consequence of ruptured LA. Along with the clinical signs of icterus, right upper quadrant pain, and a history of loose stools, patients present with non-specific symptoms such as fever, nausea, and generalized weakness. Consistent findings include male sex prevalence and frequent alcohol consumption. Leukocytosis, abnormal liver function, and an increased international normalized ratio have been identified by biochemical analysis; however, these findings are not specific to a ruptured LA diagnosis, and imaging is necessary to reach a definitive diagnosis. Ultrasonography usually confirms the diagnosis, and computed tomography is required in certain situations. In confined ruptures, percutaneous drainage combined with antibiotic therapy is typically the initial treatment course. Generally reserved for non-responders or moribund patients with delayed presentation, an open surgical approach may involve simple draining of a ruptured abscess or ileocecal resection, or right hemicolectomy in cases of large bowel perforations, both of which increase patient morbidity. A definite guide to management is still missing in the literature. In this article, we have discussed and correlated with data the predictors of surgery and preoperative predictors of perforation. Materials and methods This retrospective study was performed at Safdarjung Hospital, New Delhi, between January 2022 and December 2023. The study included 115 patients diagnosed with ruptured LA by ultrasound. Medical records were analyzed, and various parameters of the illness, clinical features, hematological and biochemical profiles, ultrasound features, and therapeutic measures were noted and assessed. Results Of the 115 patients, 88% (n = 101) were male. The most common symptoms were abdominal pain (114 patients) and right upper abdominal tenderness (107 patients). Fifty-two patients were treated with percutaneous drainage, and 42 underwent laparotomy. Intercostal drainage (ICD) tubes were placed in 19 patients. Sixteen patients had large bowel perforations. Twenty-three patients died (20%), including 17 patients who underwent laparotomy and nine patients who had large bowel perforation (39.1% associated with overall mortality, 52.9% associated with mortality in laparotomy). One patient with percutaneous drainage and a right ICD tube died in the intensive care unit. Four patients died before intervention. Significant associations were noted between perforation and mortality in patients who underwent surgical drainage. Loose motions, alcohol and smoking consumption, and deranged creatinine and albumin levels were found to have a significant association with surgical drainage. Conclusion The study found that a ruptured liver abscess (LA) may require surgery to drain the collection or repair the pathological bowel, which increases the morbidity, but it is a lifesaving procedure over percutaneous catheter drainage. The study also identified factors associated with a higher risk of death, such as a history of loose stools and low blood albumin levels.


Introduction
The first recorded cases of liver abscess (LA) date back to 400 B.C. in ancient Greece, when Hippocrates believed that the sort of fluid in the lesion would determine patient outcome.One potentially fatal consequence of bacterial, fungal, protozoan, and worm infections is LA, a confined, frequently encysted, purulent inflammation with parenchymal necrosis [1].LAs have a mortality rate of up to 20% and are classified into different categories based on their origin, and the two most common varieties are pyogenic LA (PLA) and amebic LA (ALA) [2].The peritoneal cavity is the most common location of ruptured LA, a serious surgical emergency [3].
Most LAs are observed in the right hepatic lobe and may be solitary or multiple.One of the following five methods of liver infection dissemination can be found in most LA cases: hematogenic, through the hepatic artery, portal vein, or umbilical vein in severe septic processes as in metastatic-pyemic LA or portal vascular thrombosis and occasionally as in omphalophlebitis; biliary, through the biliary tract in cases of cholecystitis or cholangitis, as well as from invasion by parasites (oriental cholangitis) or foreign bodies; by continuation, the spread of inflammatory processes to the liver from surrounding areas; post-traumatically, traumatic liver injuries or as a result of an intrahepatic hematoma; and postoperatively [1].
The primary cause of LA is appendicitis; however, with improved detection and treatment, the incidence of this condition has greatly declined.Currently, the main causes of PLAs include biliary tract disorders (biliary stones, strictures, malignancies, and congenital defects) [4].The cause of a hepatic abscess may be difficult to determine, as the most common cause is cryptogenic.This is seen in 69% of all cases of LA, commonly presenting with comorbidities such as diabetes mellitus (60.9-68% of cases), coronary artery disease, chronic obstructive pulmonary disease, malignancy, or liver cirrhosis [5].Blood tests are not diagnostic for LAs.However, leukocytosis and elevated alkaline phosphatase (ALP) levels are common findings [6].Although there are no specific clinical criteria for differentiating between PLA and ALA, a differential diagnosis can be established using the following criteria: clinical suspicion of ALA increases with younger age, residency, or recent travel to locations with endemic amebiasis, diarrhea, and severe stomach discomfort [7].LA rupture is a rare occurrence, with a prevalence of 5.4% [8].Patients with LA often have non-specific constitutional symptoms when they first present, and their clinical presentation is atypical.The most frequent symptoms are fever and chills, followed by pain in the right upper quadrant and hepatic tenderness [9].
Compared with other LA etiologies, there is a higher incidence of abscess rupture in patients with Klebsiella pneumoniae PLA, notwithstanding the rarity of spontaneous LA ruptures.Persistent hyperglycemic dysregulation in patients with diabetes, large abscess size >5 cm, thinned wall, and gas-forming abscesses (pain limited to the right upper quadrant and hepatic tenderness) are suggested risk factors for spontaneous rupture in K. pneumoniae PLA [10].
When treatment is neglected and the diagnosis is delayed, a significant mortality rate of 75% has been seen [11].Imaging remains essential for the diagnosis of ruptured LAs because it allows positive and topographic diagnoses.Surgery is always associated with medical treatment and remains the best option for cases of peritoneal cavity rupture.However, conservative percutaneous drainage with appropriate antibiotic therapy may be sufficient for localized rupture of the pleura, pericardium, or abdominal wall [12].
Any drainage strategy must include antibiotic medication because it plays a vital role.Given that E. coli, K. pneumoniae, and other Enterobacteriaceae have up to 30% resistance rates to fluoroquinolones, thirdgeneration cephalosporins (ceftriaxone and cefotaxime) and piperacillin/tazobactam have solidified their leading positions in the treatment of PLA with antibiotics.Therefore, the first antibiotic regimen should consist of piperacillin, tazobactam, or third-generation cephalosporins and metronidazole.The latter has the advantage of partially covering enterococcal infections [10].Based on available data, combined therapy involving an aminoglycoside and a beta-lactam antibiotic is recommended for individuals with severe infections caused by Klebsiella spp.and hypotension [13].Carbapenems are recommended for treating extended-spectrum β-lactamase-producing K. pneumoniae and E. coli.Compared to other antibiotics, the use of carbapenems, particularly imipenem/cilastatin, is independently associated with lower mortality [14].The increasing prevalence of K. pneumoniae strains resistant to carbapenems, such as those that produce the New Delhi metallo-beta-lactamase-1 or K. pneumoniae carbapenemases, is a concern because of the limited treatment options available for these hyperresistant strains, including tigecycline, colistin, and aminoglycosides.These strains are also associated with increased mortality [15].Shorter antibiotic courses consisting of targeted intravenous therapy for two to three weeks and sequential oral therapy for one to two weeks have been linked to exceptionally low mortality rates of less than 5% in certain studies conducted in the USA.In cases of ALAs, metronidazole is an excellent agent, and most patients respond to therapy within 72-96 hours [16].Studies have shown that percutaneous drainage should be considered the first choice, even in cases of multiple LAs, as it has demonstrated shorter hospitalization and lower costs than surgical drainage (laparotomy) [17].

Study design and patient selection
We retrospectively studied patients admitted to Safdarjung Hospital, New Delhi, India, between January 1, 2022, and December 31, 2023, reviewing the electronic medical records of patients with ruptured LAs.The inclusion criteria were as follows: confirmed LA (at least one space-occupying lesion in the liver) [1] through ultrasonography (USG) and patients aged >12 years.The exclusion criteria included outside-operated patients and those with missing data.This analysis included 115 patients with ruptured LAs.Data on demographics (sex and age), duration and unit of hospitalization, clinical manifestations (pain, fever, jaundice, loose motions, obstipation, tenderness, peritonitis, melena), laboratory findings, and imaging at admission, comorbidities (diabetes mellitus, hypertension, and chronic liver diseases (CLDs), including hepatitis B and C), and alcohol consumption were collected.Routine blood examinations included a complete blood count, serum biochemical tests (including liver and renal function tests), coagulation profile, and serum albumin levels.Sepsis and septic shock were defined according to International Sepsis Definitions Conference criteria.Fever was defined as an ear temperature of >37.8 °C.Multiple LAs were defined as abscesses ≥3.

Treatment and outcomes
We collected data on the duration of inpatient intravenous antimicrobial therapy, surgical procedures performed, and pigtail (percutaneous USG-guided) drainage.Empirical antibiotic therapy included thirdgeneration cephalosporins, piperacillin-tazobactam, and metronidazole.The evaluated treatment outcomes included antimicrobial therapy combined with percutaneous catheter drainage (PCD), surgical treatment, and intercostal chest tube drainage.The definition of PCD failure included death when an abscess drain was in place or when surgical treatment was required [15].The need for surgical treatment was evaluated based on clinical expertise, an assessment of biochemical parameters, and hospital guidelines.Mortality included deaths that occurred in-hospital within 30 days of initial hospitalization.The cause of mortality was death as a direct consequence of PLA or its complications.

Statistical analyses
All data were analyzed using the IBM SPSS Statistics for Windows, Version 28 (Released 2021; IBM Corp., Armonk, New York, United States).Descriptive analysis was used to compare the differences in demographics, clinical manifestations, laboratory factors, and treatments (surgery and pigtail insertion).Continuous variables were presented as means (standard deviations (SDs)), while categorical data were presented as numbers (n) and percentages (%).Independent two-sample t-tests were used to analyze continuous variables.Categorical variables were compared using chi-square or Fisher's exact tests.The relationships among demographic characteristics, clinical manifestations, laboratory factors, and outcomes were assessed using univariate analysis.Multivariate logistic regression models in the forward selection mode were applied to significant factors from the univariate analysis.All statistical tests were two-sided, and a p<0.05 was considered significant.

Clinical and laboratory findings
Abdominal pain was the most common symptom (114 patients), and the average number of days of abdominal pain before the presentation was 14, with a median of 10 days (Table 3).Fever, jaundice, loose motions, and obstipation were present in 89 (77.3%), 29 (25%), 18 (15.6%),and four (3.4%) patients, respectively (Figure 3).Diabetes was present in 10 (8.6%) patients, 45 (39%) patients reported alcohol usage, and 26 (22.6%) patients had a history of smoking (Table 4).Eight patients were diagnosed with CLD, and one patient had a hepatitis C virus infection.Three patients had hypertension during treatment, and 12 (10.4%)patients had tuberculosis.

Management, treatment, and outcomes
Five (4.3%) patients were discharged after receiving intravenous antibiotic treatment (Figure 5).Fifty-two (45.2%) patients underwent USG-guided percutaneous drainage, and one patient underwent USG-guided aspiration.Forty-two (36.5%) patients underwent surgery (exploratory laparotomy) (Table 10).Sixteen (13.9%) patients had large bowel perforations (Table 11).Nine patients had cecal perforation, three patients had cecal and ascending colon perforation, and one patient had hepatic flexure perforation.Three patients had isolated transverse colonic perforations (Table 12).Two patients underwent laparotomy after unsuccessful percutaneous drainage.An intraoperative pleural rupture was observed in one patient.Nineteen patients required thoracic drainage (intercostal drainage (ICD) tube), seven required percutaneous drainage and ICD, and three required laparotomy and ICD.Twenty-three (20%) patients were reported dead, including 17 patients who underwent laparotomy and nine patients who had large bowel involvement/perforation (39.1% associated with overall mortality, 52.9% associated with mortality in laparotomy).One patient who underwent percutaneous drainage and a right ICD tube placement was admitted to the intensive care unit.Four patients were declared dead before any intervention could be performed, representing 17.3% of the total 23 mortality cases, which is 3.4% of the total 115 patients included in this study, which signifies the severity of the disease at presentation.In one patient, the ICD tube was secured, given respiratory distress.

Predictors of surgical drainage
Surgery was performed in 42 patients, and the associations between surgery and clinical, biochemical, and radiological parameters were evaluated.

TABLE 15: Association of clinical, biochemical parameters with mortality in cases of ruptured liver abscess
The data are presented as percentage (%), total number (n), and mean±SD, and p<0.05 indicated significance.

TABLE 17: Association of clinical parameters with perforation
The data are presented as percentage (%), total number (n), and mean±SD; p<0.05 was considered significant.

CXR: chest X-ray
A total of 23 mortalities were recorded, of which 11 (68.8% of perforation cases) were found to involve perforation, and five patients with perforation survived with prompt management (p = 0.000).

Ruptured abscess status on USG
A ruptured LA, other than systolic blood pressure, was reported on USG in 105 patients, and no significant association was found between demographic, clinical, and biochemical parameters (Table 18).

TABLE 18: Correlation of ruptured status on USG abdomen with clinical and biochemical parameters
The data are presented as percentage (%), total number (n), and mean±SD, and p<0.05 was considered significant.

Discussion
Ruptured LA is an uncommon complication of LA, and this current study showed a 20% mortality rate for cases that were not diagnosed promptly and treated appropriately, which was less than the 43% reported by Chou et al. [8].The 20% mortality rate reported in patients with ruptured LAs in this study was higher than the rate reported in a study by Ibarra-Pérez [18].The hospital where this study was conducted is the major referral center that receives patients from all over India, and some of these referrals have a late presentation of the disease, which may account for this difference (high mortality rate).The natural course of an LA is rupture, which can be fatal if left untreated.
Of the 115 patients in this study, 88% were male.Abdominal pain was the most common complication in our study, with a median presentation time of 14 days, as reported by Rajak et al. [19].Common comorbidities observed in patients with LAs include diabetes mellitus, hypertension, malignant tumors, biliary stones, a history of abdominal surgery, liver cirrhosis, and alcoholism [20].In our study, 40% of the population consumed alcohol.The following mechanisms have been proposed for the ALA predisposition to alcohol: alcohol suppression of Kupffer cell function, which plays an essential role in clearing the ameba; hepatocyte damage by alcohol; hepatic accumulation of iron; alcohol-facilitated invasive capacity of Entamoeba histolytica (EH); nutritional deficiency-induced lowered body resistance and suppression of liver function in patients who consume alcohol; alcohol-associated depression of immune activity; and facilitation of EH entry into the blood by dysbiosis of intestinal bacteria and alcohol-induced intestinal hyperpermeability [21].
Abdominal pain was the most common complaint, followed by fever, jaundice, and loose motions, which matched the results of other studies where fever was the most common presentation and was seen in 91% of patients, followed by abdominal pain in 86%, loss of appetite in 43%, jaundice in 36%, nausea and vomiting in 20%, and a few other symptoms, including cough, expectoration, loose motions, and abdominal mass.These findings are in line with those of Ochsner et al., who reported that 94% of their study population suffered from fever, 92% experienced abdominal pain, and 33% had nausea and vomiting [22].Greenstein et al. observed that 95%, 84%, 42%, 39%, and 24% of patients with LAs had a fever, abdominal pain, abdominal tenderness, hepatomegaly, and jaundice, respectively [23].In our study, LAs were confined to the right lobe in 76% of the cases, which is in agreement with the study conducted by Sharma et al. [24].
Leukocytosis, elevated ALP levels, anemia, and an atypical INR are common laboratory findings in ruptured abscesses.Pleural effusion was observed in more than 50% of the cases.A ruptured abscess requires drainage; 45.2% of the patients responded to percutaneous drainage, and 36.5% of the patients required surgical management.Only two patients had failed PCD; they underwent surgical drainage.In our setting, if a patient is in shock with features of peritonitis, a USG diagnosis of a ruptured LA is indicated for an emergency exploratory laparotomy.Patients with leukocytosis, stable vitals (only tachycardia and fever), and right upper abdominal tenderness underwent percutaneous drainage, with a daily assessment of drain output and the development of sepsis.Patients with only abdominal pain, a USG diagnosis of ruptured LA, and a near-normal biochemical profile are candidates for USG-guided pigtail/percutaneous drainage.
We recognize that the retrospective nature of our study serves as a limitation.Our information was restricted to what was documented in the medical files.Nonetheless, no notable distinction existed in the absent assessments at admission between the groups with and without case fatalities.The potential impact of the non-random effect of missing data on the research findings was reduced to a minimum.In our study, serum creatinine was a significant prognostic factor for mortality, which is consistent with previous findings [25].In a few studies, age, blood pressure, white blood cell count, hematocrit, serum creatinine levels, and underlying medical conditions (malignancy, liver cirrhosis, and uremia) were independent predictors of mortality, as shown in our study.As microbiological examinations were not performed in our study, the risk of K. pneumoniae, gas-forming abscesses, and associated complications (such as thrombocytopenia and endophthalmitis), which can affect mortality, was not assessed.
In a study published in India in the 1970s, Monga et al. described two patterns of rupture associated with amebic peritonitis [26].They were convinced that rupture cases could be managed conservatively, whereas free rupture (intraperitoneal spread) required open drainage.Subsequently, a new study reportedly showed that the two distinct patterns affected the outcome and that a conservative approach was sufficient to manage localized intraperitoneal fluid collection; however, 50% of cases with generalized peritonitis in their study required surgery [27].
In our study, 45.2% (n = 52) of the patients underwent percutaneous drainage, and only two reported treatment failure, which was in line with the study conducted by Sohn et al. [28].This study also considered the outcomes of patients who underwent percutaneous drainage, as more than 50% were treated with the same modality, with a decreased total duration of hospital stay.At our institute, PCD is the treatment of choice for uncomplicated ruptured LAs.
A limitation of this study is its retrospective nature and single-center design, which can only help to create a hypothesis regarding the factors significantly associated with perforation and mortality and the patients that might require open surgical drainage.Therefore, further prospective trials are required to confirm this hypothesis.Nevertheless, our study has some strengths.First, it adds to the factors already defined in the literature and provides an in-depth analysis of the factors associated with surgical drainage and bowel perforation linked to ruptured LAs.
Depending on the type of rupture, these authors attempted to make recommendations regarding the appropriate surgery for ruptured ALA.However, the mortality associated with surgery in the management of amebic peritonitis remained high and was reported to be up to 50% in a study by Priyadarshi et al.All free rupture cases were treated with catheter drainage; however, they required multiple catheters and longer hospital stays, and they showed that incomplete drainage in 50% of the patients was helpful in relieving peritonitis.Thus, complex septation does not preclude PCD as a therapeutic option for ALA rupture in generalized peritonitis.An intercostal chest tube may be required if empyema is suspected because of pleural communication of a ruptured abscess or massive pleural effusion causing respiratory distress.

Conclusions
A ruptured LA is a surgical emergency with varied clinical presentations, from only abdominal pain to features of perforation, peritonitis, and shock.Cryptogenic LAs are the most common.Males were most affected, usually involving the middle-aged group (the median age in our study was 45 years).Alcohol consumption is a major risk factor for LAs.Early recognition of clinical symptoms and prompt investigation and treatment of sick patients were prognostic indicators.Tenderness, peritonitis, loose motion, increasing age, increased creatinine, leukocytosis, low albumin levels, and a history of CLD were independent predictors of mortality.Prompt treatment should be initiated, and adequate resuscitation should be performed to prevent and decrease LA-associated mortality.Jaundice, history of loose motion, alcohol consumption, fever, and CLD were significantly associated with perforation; caution should be taken in these cases, and prompt surgical intervention should be performed to correct the underlying pathology.USG-guided percutaneous drainage is the preferred treatment for stable patients without peritoneal features.Surgical management and exploratory laparotomy are life-saving procedures performed on an emergency basis to reduce the source and ensure adequate abscess drainage.Good knowledge of the symptoms, signs, and biochemical profiles can guide early treatment.

FIGURE 4 :
FIGURE 4: Distribution of ruptured collection

FIGURE 5 :
FIGURE 5: Distribution of management options in patients with ruptured liver abscess PL: peritoneal lavage; iv: intravenous

TABLE 3 : Chief complaints of the study population
(N = 115) FIGURE 3: Distribution of chief complaints (N = 115)

TABLE 4 : Comorbidities of the study population (N = 115)
Right upper quadrant tenderness was the most common clinical finding present in 106 (92.1%) of the 115 patients, and three patients presented with shock.Generalized guarding and peritonitis were present in 30.4% (n = 35) of the patients.

TABLE 5 : Biochemical parameters of the study population (N = 115)
ALP: alkaline phosphatase; TLC: total leukocyte count; SD: standard deviation; PT/INR: prothrombin time/international normalized ratioCharacteristics of ruptured LA and collectionOn the USG, 79 (68.6%) patients had a single cavity.The right and left lobes were isolated in 88 (76%) and 11 (9.5%) patients, respectively (Table6, 7).Combined right and left lobe involvement was observed in 12 (10%) patients.Subcapsular collection with rupture was present in 45 (39.1%) patients; other locations were perihepatic in eight patients, subdiaphragmatic in 18 patients, subhepatic in four patients, peritoneal in nine patients, and intrathoracic in 10 patients, with 8.6% having a pleural connection (

TABLE 8 : Ultrasound findings in the location of ruptured liver abscess
USG: ultrasonography

Table 9
).The average volume of LA collection recorded on USG was 292 cc, with a maximum of 1,500 cc recorded in one patient.Moreover, 103 (89%) patients were diagnosed with ruptured LAs, as rent was visible along the cavity wall.(%)